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journal article·2026-07-11Open access

Targeting GALNT7 Disrupts the TAZ O‐GalNAcylation Feedback Loop to Suppress Gallbladder Cancer Progression

Peng Qiu, Ming Zhang, Yunxiang Feng, Yibo Deng, Kai Zhao, Xiangyu Li, Yun Lu, Li Tian, Tao Yang, Wei Yao, Jianming Wang, Zhengdong Deng

Advanced Science
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Source abstract

Abstract

ABSTRACT Gallbladder cancer (GBC) is a lethal malignancy with limited therapeutic options and dismal prognosis. Identifying the factors driving GBC progression is crucial for developing potent preventive and therapeutic approaches. Here, using quantitative proteomics, we identify GALNT7 as the most significantly upregulated glycosyltransferase in GBC tissues, associated with adverse clinical outcomes. Mechanistically, GALNT7 physically interacts with TAZ and catalyzes O‐GalNAcylation at Ser307, thereby inhibiting K48‐linked ubiquitination through the recruitment of the deubiquitinase USP7 and stabilizing the TAZ protein. This post‐translational modification promotes TAZ accumulation and subsequent activation of TEAD1‐mediated transcription, which in turn upregulates GALNT7 expression, thereby establishing a self‐reinforcing oncogenic feedback loop. Disruption of TAZ O‐GalNAcylation via the S307A mutation abrogates its oncogenic activity and attenuates GALNT7‐driven tumor progression. Importantly, structure‐based drug‐repurposing screens identified the PARP inhibitor Olaparib as a direct GALNT7 antagonist that effectively inhibits TAZ O‐GalNAcylation and demonstrates potent anti‐tumor efficacy against GBC both in vitro and in vivo. Collectively, our findings reveal a glycosylation‐dependent regulatory axis that drives GBC progression and establish GALNT7‐TAZ signaling as a tractable therapeutic target.
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Research context

CompositesCatalysis & surfaces

OpenAlex topics: Hippo pathway signaling and YAP/TAZ · Microtubule and mitosis dynamics · Ubiquitin and proteasome pathways

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Division of Hepato‐Pancreato‐Biliary Surgery Tongji Hospital Tongji Medical College Huazhong University of Science & Technology Wuhan Hubei P. R. China

Hubei Key Laboratory of Hepato‐Pancreato‐Biliary Diseases Wuhan Hubei P. R. China

Clinical Medicine Research Centre for Hepatic Surgery of Hubei Province Wuhan Hubei P. R. China

Clinical Medicine Research Centre for Pancreatic Surgery of Hubei Province Wuhan Hubei P. R. China

Department of Thoracic Surgery Affiliated Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan Hubei P. R. China

Department of Geriatrics Affiliated Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan Hubei P. R. China

Department of Pediatric Surgery Affiliated Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan Hubei P. R. China

Department of Hepatobiliary Surgery Renmin Hospital of Wuhan University Wuhan Hubei P. R. China

Department of Oncology Affiliated Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan Hubei P. R. China

Affiliated Maternal and Child Health Hospital of Hubei Province Tongji Medical College Huazhong University of Science and Technology Wuhan Hubei P. R. China

Funding

National Natural Science Foundation of China

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